Interpretive Summary: Hepcidin is a hormone produced by the liver that is believed to regulate the levels of iron in the body. In a study with rats, hepcidin amounts were inversely associated with iron absorption. This study was to test whether this held true in human studies. Prohepcidin, a precursor to hepcidin, was also studied since the small size of hepcidin may present some problems with measurements. Serum levels of hepcidin and prohepcidin were measured after human subjects were given iron either as ferrous sulfate or in a food matrix (orange sweet potato). A second objective of the study was to see if the relationship between hepcidin and iron absorption was the same whether the iron came from a supplemental iron (ferrous sulfate) or a food matrix. Therefore, different forms of stable iron isotope was added to the ferrous sulfate and sweet potato so the amount and source of the iron could be differentiated. The results suggest that serum hepcidin, but not prohepcidin, was inversely associated with iron absorption from supplemental and food-based nonheme-iron sources in iron-replete healthy women.

Technical Abstract:
Hepcidin is a key regulator of iron homeostasis, but to date no studies have examined the effect of hepcidin on iron absorption in humans. Our objective was to assess relations between both serum hepcidin and serum prohepcidin with nonheme-iron absorption in the presence and absence of food with the use of dual stable iron isotope techniques. The study group included 18 healthy nonpregnant women. Women received in random order a supplemental iron source (8.5 ½AQ2_ mg of ferrous sulfate providing 0.9 mg of 58Fe as ferrous sulfate) and 6.8 mg of 57Fe ferrous sulfate tracer administered with a nonheme food source [orange-fleshed sweet potato (OFSP): 1.4 mg ½AQ3_ native iron]. Iron absorption was determined by analyzing blood samples taken 14 d after dosing with the use of magnetic sector thermal ionization mass spectrometry. Serum hepcidin was assessed by a new competitive serum enzyme-linked immunosorbent assay (ELISA) specific for the refolded, mature 25-amino acid form, and serum prohepcidin was assessed by an ELISA specific for amino acids 28–47 of the hepcidin prohormone. In these women, iron absorption averaged 14.71 6 10.7% from the supplemental iron compared with 3.63 6 6.5% from the OFSP. Absorption of nonheme iron assessed in the presence (P ¼ 0.038) and absence (P ¼ 0.0296) of food was significantly associated with serum hepcidin but was not significantly related to serum prohepcidin.
Conclusion: Serum hepcidin, but not prohepcidin, was inversely associated with iron absorption from supplemental and food-based nonheme-iron sources in iron-replete healthy women.